1. Field of the Invention
The present invention relates to a hyaluronic acid epoxide derivative film, and more particularly to a hyaluronic acid epoxide derivative film which is prepared by allowing an epoxide crosslinker to react with a mixture of hyaluronic acid and a polymer containing a hydroxyl (—OH) terminal group and has improved physical strength, in vivo stability, flexibility, adhesiveness to biological tissue, and biocompatibility.
2. Description of the Prior Art
Hyaluronic acid which was first isolated from vitreous humor by Meyer and Palmer in 1934 is a polyanionic mucopolysaccharide and is a biopolymer that is widely found in nature (Meyer K. et al., Journal of Biology and Chemistry 107 629-34 (1934)). Hyaluronic acid is abundantly found in animal placentae, eyes, and connective tissues such as joints, and is also produced in Streptococcus sp. microorganisms, Streptococcus equi, Streptococcus zooepidemicus and the like. It has a structure in which repeating units of glucuronic acid and N-acetylglucosamine, which are linked by β(1,3) glycosidic bonds, are continuously linked to each other by β(1,4) glycosidic bonds to form a long chain structure (Balazs E. A. et al., Biochemical Journal, 235, 903, 1986; Toole B. P. et al., Journal of Internal Medicine, 242, 35-40 (1997)).
Hyaluronic acid has excellent biocompatibility and is highly viscoelastic in a solution state. Thanks to such properties, hyaluronic acid is widely used not only in cosmetic applications, including cosmetic additives, but also in various pharmaceutical applications, including ophthalmic surgical aids, joint function-improving agents, drug delivery materials, and eyedrops. However, because hyaluronic acid is easily degraded in vivo or under acidic or alkaline conditions, the use thereof is limited. Thus, there have been many efforts to develop structurally stable hyaluronic acid derivatives (Laurent T. C. et al., Portland Press Ltd., London, 1998).
Hyaluronic acid derivatives have excellent biocompatibility, physical stability and biodegradability, and thus have been developed for use in various applications, including implants for plastic surgery, joint function-improving agents, drug delivery materials, cell culture scaffolds, and materials for preventing post-surgical adhesion.
Among methods for obtaining hyaluronic acid derivatives, methods employing epoxide crosslinkers have been developed to provide products in various forms, including solutions, gels, fibers, sponges and films. Methods for producing these products are disclosed in U.S. Pat. Nos. 4,500,676, 4,713,448, 4,716,224, 4,716,154, 4,886,787, 4,963,666, 5,827,937, etc.
However, the hyaluronic acid epoxide derivative films have problems in that shrinkage occurs during drying, making it difficult to produce uniform films, and in that the physical strength of the films is reduced during purification.
In an attempt to overcome these problems occurring in the production of the hyaluronic acid epoxide derivative films, Korean Patent Laid-Open Publication No. 2009-0012439 discloses a film having improved flexibility and physical strength, which is produced by surface crosslinking of hyaluronic acid (HA) and carboxymethylcellulose (CMC). However, if the content of HA is increased, the film will have low physical strength, and thus will be rolled up in a wet state, and if the content of CMC is increased, the film will have a slow biodegradation rate so that it will remain for a time longer than required, thus causing foreign body reactions.